EPIDEMIOLOGY
The Face of CFS in the U.S.
What does the face of chronic fatigue syndrome look like? Is it male or female,
adult or child, Caucasian, African American or Latino? Is it the face of someone
who has been ill for 15 months or 15 years? Is it someone who became ill suddenly
or gradually? Read on for what we know so far.
By Leonard A. Jason, PhD, Susan R. Torres-Harding, PhD, and Mary Gloria C. Njoku, MA, DePaul University
The epidemiology of chronic fatigue syndrome
(CFS) has stimulated significant interest and
controversy within the scientific community since
the mid-1980s. Because reliable epidemiological
data can be invaluable in advancing
understanding of the etiology,
diagnostic validity, basic prevalence and the long-term course
and prognosis of many poorly
understood conditions, including CFS, epidemiology is a
critical focus in unraveling the
complexities of this illness.
Although this research
focus on CFS is relatively recent,
chronic fatigue syndrome is not a
new phenomenon. Severe fatigue
illnesses of unknown origin have been
reported for more than 150 years in
countries across the world.1 The
diagnosis of these illnesses has
varied considerably, depending
on the predominant symptoms,
country of origin and other
factors. Across the world,
these fatigue illnesses have
been labeled epidemic neuromyasthenia, myalgic
encephalomyelitis (ME), atypical
poliomyelitis, post-polio syndrome,
chronic encephalomyelitis and various
other names, with no universally accepted
diagnostic criteria to determine if the same illness
was responsible for some, or many, reported cases.
The emergence of chronic Epstein-Barr virus
syndrome and two cluster outbreaks during the
2 0 0 5
–
2 0 0 6
1980s—184 cases in Lake Tahoe, Nevada, and 214
cases in upstate New York—renewed interest in
fatigue illnesses in the United States. These outbreaks eventually led to the involvement of the
Centers for Disease Control and Prevention (CDC), which named the illness
chronic fatigue syndrome (CFS) and
created a U.S. case definition for
diagnosis in 1988.2 That case
definition was refined in 1994
by an international consensus
group, and it is this definition,
commonly called the Fukuda
definition, that forms the
basis for most current research
in the U.S.3
However, there are other case
definitions, including the Ramsey
definition, the first true case definition,
which was developed in England in
1981; the London criteria of 1992;
the Australian case definition;
and the 2004 Canadian consensus definition.4,5 Unfortunately,
the criteria differ, clouding the
diagnostic, epidemiological and
etiological picture worldwide
and making many research
comparisons difficult.
There is a need to conduct
studies that contrast and compare
different CFS case definitions and to further
refine the criteria based on the results of this
research. One universally accepted case definition,
both for diagnostic and research purposes, would
help uncover the face of CFS.
The Science & Research of CFS
How many Americans have CFS?
In the United States, we have been trying to
paint an accurate epidemiological picture of CFS
since 1988, less than 20 years. Early studies,
including physician-based surveillance studies,
significantly underestimated the prevalence of
CFS. Over time, new epidemiology studies were
undertaken, leading to dramatic increases in
prevalence estimates and refinements in study
methodology. Here is a rundown of key first- and
second-generation studies:
The first widely publicized study of CFS
epidemiology was done by the CDC in the late
1980s. Prevalence rates of CFS were found to range
from 4.0 to 8.7 individuals per 100,000 cases,
but the study only included information from
physicians in four cities who identified patients with
specific fatigue-related symptoms.6
In 1993 DePaul University researchers
interviewed a random community-based sample of
adults in Chicago.7 The research team found 200
individuals per 100,000 with CFS, which was considerably higher than the rate originally reported by
the CDC. The sample size for this study, however,
was relatively small, with only 1,031 participants.
The CDC conducted a community-based survey
in San Francisco in 1994.8 Investigators contacted
8,004 random households by phone, obtaining
information on 6,970 adult and minor residents.
Researchers estimated the prevalence of CFS-like
illness to be between 76 and 233 per 100,000.
Unfortunately, medical and psychiatric evaluations
weren’t included in this study, so it’s not known
how many of the people who reported the
symptoms of CFS would actually meet the
criteria after completing a medical evaluation.
In 1995 Buchwald and associates found rates
from 75 to 267 per 100,000 in a sample of
individuals enrolled in an HMO.9 Because
respondents all had access to an HMO, individuals
lacking access to the health care system were
underrepresented.
The DePaul research team conducted a larger
community-based study from 1995 to 1998,
contacting households in Chicago by telephone.10
Some 18,675 individuals were screened for CFS
symptoms, and individuals who self-reported
symptoms of CFS were asked to complete a medical
workup to determine whether they fully met the
1994 Fukuda criteria for CFS. A prevalence rate of
Fast Facts
■
As many as 900,000 Americans have CFS according to the Centers for
Disease Control and Prevention (CDC) and research conducted by
DePaul University.
■
The phrase yuppie flu, coined in the 1980s to describe CFS, turned out
to be wrong on almost all counts. The illness occurs most often in people
aged 40-59, and it’s more common in lower-income than affluent
individuals. While most patients aren’t young, affluent professionals,
many do experience severe flu-like symptoms, so that part of the name
was correct.
■
Approximately 3 to 5 times more women have CFS than men.
■
CFS occurs in all ethnic and racial groups, and in countries around the
world.
■
Although CFS is less common in children than in adults, very little is
known about the occurrence of this illness in children. Studies suggest
CFS is more prevalent in adolescents than younger children.
■
Between 63% and 77% of adult CFS patients in community-based
samples experience gradual onset of the illness, while the remainder
become ill suddenly and can often name the exact day their lives
changed because of this illness.
■
According to a CDC study, only 16% of Americans with CFS have been
diagnosed, a staggering statistic. In a community-based study in
Chicago, the rate was even lower, with only 9% diagnosed.
420 per 100,000 was found. Given U.S. Census data
of the time, investigators estimated that approximately 800,000 American adults had CFS in 1999.
In the largest population-based prevalence study
to date, nearly 25% of the population of Sedgewick
County (Wichita), Kansas was surveyed, with
34,000 households called.11 Data from this Wichita
cohort led CDC investigators to increase estimates
of CFS prevalence rates to 235 per 100,000.
In 2001 Herrell examined CFS-like illness in
American Indian tribes and in Mexican American
populations of Fresno County, California, finding
prevalence rates of 200 to 400 per 100,000.12
Unfortunately, medical examinations didn’t occur
with these surveys, so it’s unclear whether similar
rates would have been found for CFS.
Because the Fukuda case criteria are very
strict, people with CFS-like illness are excluded
from prevalence estimates. Even though those
individuals don’t meet the strict case definition,
CFIDS
C H R O N I C L E
EPIDEMIOLOGY
International Prevalence of CFS
Chronic fatigue syndrome is found all over the world. Just like in the
United States, CFS prevalence estimates vary dramatically. Here are
some representative samples.
Japan:
0.85 cases per 100,000 (Minowa and Jiamo, 1996)
1,500 cases per 100,000 (Kawakami, Iwata, Fujihara & Kitamura, 1998)
Hong Kong:
Australia:
3,000 cases per 100,000 (Lee et al, 2000)
37.1 cases per 100,000 (Lloyd, Hickie, Boughton, Spencer, Wakefield, 1990)
1,500 cases per 100,000 (Hickie, Koschera, Hadzi-Pavlovic, Bennett & Lloyd, 1999)
New Zealand:
Brazil:
127 cases per 100,000 (Murdoch, 1987)
2,000 cases per 100,000 (prolonged and severe fatigue, not CFS; Nacul et al, 1998)
Great Britain:
160 cases per 100,000 (David et al, 1990)
130 cases per 100,000 (Ho-Yen & McNamara, 1991)
2,500 cases per 100,000 (McDonald, David, Pelosi & Mann, 1993)
6 cases per 100,000 (Pawlikowska et al, 1994)
560 cases per 100,000 (Lawrie & Pelosi, 1995)
2,600 cases per 100,000 (with comorbid disorders; Wessely et al, 1997)
500 cases per 100,000 (excluding comorbid disorders; Wessely et al, 1997)
740 cases per 100,000 (Lawrie, Manders, Geddes & Pelosi, 1997)
800 cases per 100,000 (Viner & Hotopf, 2004)
Netherlands:
112 cases per 100,000
(Bazelman et al, 1999)
Iceland:
1,400 cases per 100,000
(Lindal, Stefansson & Bergmann, 2002)
t
Ialy:
9,500 cases per 100,000
(Conti et al, 1994)
they are frequently as ill as people with the formal
diagnosis. The CDC currently estimates there are
up to 900,000 Americans with CFS and another
2.5 million with CFS-like illness.
While there is still a wide variation in
prevalence estimates depending on study setting,
methodology and other factors, it’s clear that CFS
is a common chronic illness and poses a significant
public health burden on the United States. In fact,
CFS is more common in this country than cervical
cancer, AIDS or lung cancer.
Demographic profile
Chronic fatigue syndrome is more common
among adults than children. Both the Chicago
and Wichita studies estimate much lower
prevalence in children and adolescents than among
adults. In fact, the Chicago study didn’t find any
cases of CFS in the group of children aged 5 to 12,
2 0 0 5
–
2 0 0 6
and the prevalence for adolescents (aged 13 to 17)
was 181 per 100,000. Among the pediatric sample
in the Wichita study, researchers estimated the
weighted prevalence of CFS to be 49 per 100,000
and found CFS-like prevalence rates to be 338 per
100,000.11 Many other estimates of child and
adolescent CFS have not included medical
examinations to appropriately diagnose the illness.
(See page 42 for more on pediatric CFS.)
Among adults, women appear to be at much
greater risk for CFS than men. In the Wichita study,
prevalence estimates of both CFS and CFS-like
illness for women were significantly higher than
those for men. This supports previous findings in
both the San Francisco and Chicago studies, as well
as many others. In fact, it’s estimated that women
are three to five times more likely to have CFS than
men. Furthermore, both the Wichita and Chicago
studies estimate CFS prevalence to be highest
among women aged 40 to 59, contrary to early
studies which suggested younger women were more
likely to have the illness.10,11
The first generation of prevalence studies
obtained their samples by asking physicians and
clinics to identify patients who had specific
fatigue-related symptoms. Consequently, the
majority of CFS cases identified were Caucasian
women who were well-educated and middle- or
high-income earners. Minorities and low-income
individuals seem to have been underrepresented
because these groups tend to have less access to
the health-care system.13
However, later randomized community-based
studies consistently show comparable or higher
levels of CFS prevalence among minorities. For
example, in the San Francisco study, Steele et al
found that, relative to Caucasians, CFS-like
illnesses were significantly elevated among African
Americans and Native Americans.8 In the Chicago
study, investigators found that the prevalence of
CFS was higher for Latinos and African Americans,
with older Latino women reporting the highest
relative severity of fatigue.10
The most recent U.S. studies also support these
findings. For instance, in the CDC’s Wichita
cohort, rates of CFS were higher among African
Americans than Caucasians.11 Similarly, when
Herrell examined CFS-like illness in American
Indian tribes and in Mexican American
populations, the resulting prevalence rates of 200
The Science & Research of CFS
to 400 per 100,000 clearly demonstrate this illness is
found among different ethnic groups at levels at
least equal to Caucasians.12
Socioeconomic factors also appear to play a role
in the disease. The San Francisco study found that
people with annual household incomes below
$40,000 had a higher prevalence of CFS-like
illness.8 Similarly, in the Chicago study investigators found that individuals with lower educational
and occupational status reported higher levels of
fatigue than those with higher educational and
occupational status.14 In fact, this study showed
that subjects from the lowest socioeconomic group
had significantly higher disability ratings than those
from the highest group. More recently, Bierl et al
reported on a national study suggesting that lower
income and education were associated with higher
levels of chronic fatigue.15
Interestingly, the data from the Chicago study
also revealed no significant relationship between
ethnicity and socioeconomic status (SES) among
those with CFS, suggesting that ethnicity and SES
are independent risk factors. In fact, when the
effects of SES, gender, age, marital status and
parental status were controlled, ethnicity
alone didn’t play a significant role
in fatigue severity.10 Thus, higher
prevalence rates and higher
fatigue levels among lowincome groups might be
due to environmental or
psycho-social risk factors—
such as limited medical
access, poor nutrition,
unemployment, discrimination
and other documented
stressors—more than strict
ethnicity.
Illness presentation
Chronic fatigue syndrome
seems to present in two distinct
ways—sudden (acute) or
gradual onset. Interestingly,
patients with sudden onset
can often name the exact day
they became ill, while
patients with gradual onset
become ill over a period of
weeks, even months. Patients
with sudden onset are more likely
to experience symptoms of an infectious nature, including fever, sore
throat, chills and tender lymph
nodes.13,16 This suggests that sudden
onset may be indicative of a
viral/infectious
illness in this subset of CFS patients.
Research data on the percentage
of patients who experience sudden
versus gradual onset varies somewhat,
but it’s more consistent than some of
the other epidemiological data. In the
Chicago study, for instance, we found
that 63% reported gradual onset of
symptoms, while the Wichita cohort
showed 77% of CFS patients with
gradual onset.10,17 Population-based
studies like these appear to have
a higher percentage of gradual onset
than tertiary care settings, where
sudden onset is more common. There
is also some evidence to suggest that
the rate of acute onset may be higher
in pediatric CFS than adult CFS.18,19
What’s the prognosis?
Demographic
characteristics of CFS
in the U.S.
CHICAGO COHORT (1999)
Prevalence per 100,000
AGE
18-29
30-39
40-49
50-59
60+
315
412
805
413
354
RACE
White
Latino
African American
Other
318
726
337
491
OCCUPATION
Unskilled/semiskilled
Skilled worker
Professional
486
701
325
WICHITA COHORT (2003)
Prevalence per 100,000
How many people recovAGE
er from CFS? Of those
18-29
who fully recover,
30-39
what characteristics
40-49
do they have in
50-59
common? How
60-69
long does the illness last? Is there
RACE
hope of recovery
White
for people who have
Nonwhite
been sick
HOUSEHOLD INCOME
a long time?
$20,000 or less
All these questions are
$20,000-$40,000
of vital interest to
$40,001 or more
patients who are struggling with CFS and
with uncertainty
about the future.
Although clinicians and
researchers are also engaged
with these questions, very few
studies have taken place to give
us a full picture of the long-term
course of the illness. CFS is
characterized by a pattern of relapse
CFIDS
50
183
465
501
130
224
300
202
280
233
C H R O N I C L E
EPIDEMIOLOGY
The High Cost of CFS
With an illness as prevalent as CFS, the economic cost can be staggering.
According to a 2004 CDC study, the illness costs every American with CFS
about $20,000 a year in lost earnings and productivity. This means CFS costs
the United States $9.1 billion a year, not counting the cost of health care or
disability benefits.
The study authors conclude, “The extent of the burden indicates that
continued research to determine the cause of and potential therapies for
CFS could provide substantial benefit both for individual patients and for
the nation.”
and remission over long periods of time, making it
even more difficult to assess
recovery rates, illness duration and factors that
may contribute to better health outcomes.
It’s still not clear how long the illness lasts in
most people. What we do know is that some people
are sick with CFS for less than 2 years, while others
are ill for decades. The median duration of CFS was
2.9 years in the Chicago study, while CFS subjects
in the CDC’s Wichita cohort had been sick
anywhere from 8 months to 44 years, with a
median illness duration of 7.3 years.10,11,16
Full recovery from CFS appears to be rare in
adults, with an average of only 5% to 10% of
subjects sustaining total remission.17 The picture
for partial remission and improvement in symptoms
is not as bleak, although the percentage of CFS
patients who experiences partial remission varies
from study to study. A 2005 article published in
Occupational Medicine, which reviewed 28 CFS
studies, found that improvement rates varied from
8% to 63%, with a median of 39.5% of CFS patients
improving during follow-up.
One of the reasons the data varies so much is
2 0 0 5
–
2 0 0 6
that there is still no standard definition of short
versus long duration, or of recovery. Some studies
use self-reported recovery, others measure vitality,
level of physical functioning and/or symptom
severity to define recovery or improvement.
Recovery rates may also vary according to the
duration of the follow-up period. The 2005 review
of CFS studies mentioned above reveals that the
duration of follow-up may be quite important in
recovery data. Given the relapsing-remitting
pattern of the illness, some patients may be in
remission at follow-up, suggesting their illness
duration is shorter than it actually is unless the
follow-up period extends for a period of years and
detects any relapses.
“The literature on prognosis of adult CFS has
been contradictory because of differing diagnostic
criteria before 1988 and variations in the definition
of improvement,” says David Bell, MD, of Primary
Care Pediatrics. “Because CFS has no objective
markers to validate symptom severity, subjective
impressions are relied on to assess outcome and are
subject to both exaggeration and denial, depending
on the coping style of participants.”
Even murkier are determinations about what
factors influence prognosis. Older age at illness
onset, greater symptom severity, gradual onset,
longer duration of illness, depression, less education,
being unemployed, higher use of sedating and antidepressant drugs, poor coping skills and a belief
that the illness is due to physical not psychological
causes have all been implicated as possible risk
factors for a poorer outcome.
Unfortunately, results haven’t been consistent
across studies. Perhaps the most which can be said
at this time is that the most consistent factors
identified so far that may lead to a better prognosis
The Science & Research of CFS
include shorter duration of illness, younger age at
onset, milder fatigue/illness severity and the absence
of psychiatric illnesses.
As sketchy as this prognosis data is, there are
important clinical implications. For instance,
enough studies agree that illness/symptom severity
is a risk factor for clinicians to conclude that
helping CFS patients manage symptoms is an
important goal. Similarly, clinicians may want to
consider evidence from studies such as the CDC’s
2003 population-based study, which found that
delayed diagnosis may be a risk factor for poor
prognosis.11 James Jones, MD, of the CDC
explains, “In the CDC’s research to date on the
clinical course of CFS, patients who were ill for two
years or less were more likely to improve, making
early detection and treatment of CFS of utmost
importance. The longer a person is ill before
diagnosis, the more complicated the course of the
illness appears to be.”
“In the CDC’s research to date on
the clinical course of CFS, patients
who were ill for two years or less
were more likely to improve, making
early detection and treatment of CFS
of utmost importance. The longer a
person is ill before diagnosis, the
more complicated the course of the
illness appears to be.”
—DR. JAMES JONES, CENTERS FOR DISEASE
CONTROL AND PREVENTION
On The Frontier
New Studies Will Advance Understanding of CFS
DePaul University researchers and the CDC are responsible for much of what
we know about the epidemiology of CFS in the U.S. They are again on the
frontier of research with two new studies.
Dr. Leonard Jason and his DePaul University colleagues were recently
awarded an NIH grant to revisit their community-based Chicago cohort to
conduct a follow-up study of CFS progression and prognosis. Research
began in the fall of 2005 on this first large study to focus specifically on the
long-term course of CFS.
In September 2005 the CDC finished gathering data from 13 counties in
Georgia. More than 7,000 people completed a telephone survey and 700
of them visited the CDC’s clinics in northeast Atlanta or Macon to provide
investigators with a rich set of data on the CFS patients identified. The
CDC and Emory University researchers will use the data to estimate the
prevalence of CFS, better pinpoint the exact nature of symptoms and
develop control and prevention strategies.
longitudinal cohorts that include socioeconomically
diverse samples so we can determine the long-term
course of the illness and identify risk factors for poor
prognosis. We also need community-based studies to
better estimate the prevalence and incidence of
pediatric CFS and determine how it compares to
adult CFS in onset, symptom severity, psychosocial
factors, prognosis and other variables.
We have learned an enormous amount about
the epidemiology of CFS in the past two decades.
First- and second-generation studies have led us to
continually assess and refine the face of CFS. Now
it’s time for the next generation of studies. ■
Moving forward
We can now see the basic shape of the face of
CFS in the United States, but the features need to
come into sharper focus for us to understand CFS
and formulate an effective response to an illness
that constitutes a major public health concern.
For instance, research suggests that subtyping
individuals with CFS for research purposes may
be particularly useful in understanding CFS
(see page 5). There is also a vital need to examine
the course of CFS over time, particularly in random,
community-based, multiethnic populations.
We need to determine the natural history of CFS in
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References
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D, Torres S. Chronic fatigue syndrome: Occupation,
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AB, Unger ER, Reeves WC. Regional distribution of
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(http://www.pophealthmetrics.com/content/2/1/1).
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WC. A population-based study of the clinical course
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Outcomes 2003;1:49. (http://www.hqlo.com/content/1/1/49).
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WC. Chronic fatigue syndrome and other fatiguing
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Journal of Adolescent Health 2004;35:34-40.
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A, Huang CF., Richman J, McCready W, Ayers PM,
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